Myo-Inositol – A Natural Ally in Slowing CKD Progression and Fighting Disease

Andrew Kowalski, MD, FASN

Introduction

Myo-inositol, a naturally occurring sugar alcohol found in many foods and produced in the human body, has gained increasing recognition in the scientific and medical communities. Once considered merely a component of cell membrane phospholipids, myo-inositol has emerged as a critical player in numerous physiological processes. Its therapeutic potential in various diseases from metabolic syndrome to neurological disorders is becoming well established. Particularly noteworthy is its role in managing CKD.

Myo-Inositol: A Brief Overview

So what is inositol and myo-inositol?

Inositol is a form of sugar that your body naturally produces to provide structure for your cells. Outside of naturally making it we can also obtain it from meat, fruits, corn, beans grains and legumes. Inositol is frequently referred to as vitamin B8, although it is not really a vitamin in the true sense. Multiple studies have shown that inositol can provide numerous important functions within the body. Mostly known for cell membrane support, redsearch has found that it has a positive effect on insulin and many chemical messengers within the brain. This has lead researchers to conclude that inostiol actually has a major role to play in the body's metabolic and mental health.

Myo-inositol is one of nine stereoisomers of inositol and the most abundant form in the human body. It acts as a precursor for inositol triphosphate (IP3), a second messenger crucial in intracellular signaling. At this time scientists have seen that myo-inositol is involved in:

• Cell membrane formation

• Insulin signal transduction

• Lipid metabolism

• Hormonal regulation

• Renal tubular function

What is even more interesting, especially within this relm is its presence in kidney cells. It has been found to be vital for osmoregulation and proper nephron functioning, making it an important molecule in renal health.

The Burden of Chronic Kidney Disease

CKD as we know has a large negative footprint across the globe affecting over 800 million people. It is a progressive and irreversible condition that contributes to systemic complications including cardiovascular disease, mineral-bone disorder, and inflammation. Conventional treatments focus on blood pressure control, glycemic management, and minimizing proteinuria. Newer medications have shown significant promise in kidney protection, but we are still in the dawn of their influence. Despite what available treatment options we have available, they often fail to halt disease progression. We as healthcare providers, scientists and thinkers need to "jump" out of our constrained box and entertain other potential options and targets to support and synergistically work with the treatments that we have currently. This gap in effective therapeutics underscores the importance of exploring new interventions—like myo-inositol.

Myo-Inositol and CKD: Mechanisms of Action

Emerging research suggests that myo-inositol may influence CKD progression through multiple pathways:

Anti-Fibrotic Effects

Fibrosis is a hallmark of CKD and kidney destruction. Myo-inositol has been shown to modulate transforming growth factor-beta (TGF-β) signaling, which plays a central role in initiating renal fibrosis. By dampening TGF-β activity, myo-inositol can reduce extracellular matrix deposition, slowing scarring and preserving kidney structure.

In one study looking at a mouse model with unilateral ureteral obstruction, inositol treatment reduced the expression of fibrosis markers such as collagen I, fibronectin, and α-SMA, and attenuated the pathological changes associated with renal fibrosis. This suggests that inositol can counteract the fibrotic processes that contribute to CKD progression. A huge win among patients and kidney specialists.

Improved Insulin Sensitivity

At this time diabetic nephropathy is the leading cause of CKD worldwide. Myo-inositol has been shown to improve insulin sensitivity, reducing hyperglycemia induced oxidative stress and therefore glomerular injury. It enhances the insulin signaling cascade and improves glucose uptake in peripheral tissues, indirectly protecting the kidneys.

In diabetic kidney disease, specifically, it has been demonstrated to ameliorate albuminuria (protein loss in the urine and a marker of worsening disease) and improve renal function by enhancing urinary creatinine and urea levels through Improved filtration. This renoprotective effect is mediated through the upregulation of mitophagy proteins and mitochondrial biogenesis. Additionally, inositol enhances mitochondrial biogenesis, which is crucial for maintaining mitochondrial health and function in renal tissues.

Reduction of Oxidative Stress

CKD is associated with increased reactive oxygen species (ROS), leading to tubular damage and inflammation. Myo-inositol enhances antioxidant defenses and reduces mitochondrial dysfunction, limiting oxidative injury to nephrons.

Anti-Inflammatory Activity

It is well documented, and still not readly talked about, that Inflammation drives CKD progression. Myo-inositol downregulates pro-inflammatory cytokines like IL-6, TNF-α, and CRP, thereby mitigating chronic inflammation and preserving renal function.

Restoration of Tubular Function

Studies have shown that inositol depletion is a biomarker and possible contributor to tubular injury. Studies have shown elevated plasma inositol levels have been correlated with CKD severity and progression, indicating its utility in early diagnosis and monitoring of the disease. Increased urinary excretion of inositol has also been associated with CKD severity, suggesting its role in renal osmolyte regulation and protection against hyperosmotic stress.

In hindsight this makes sense as one of the major roles of inositol is enhancing cell membrane structure and function. Supplementing myo-inositol may help restore cellular osmotic balance and improve solute transport mechanisms within damaged tubules.

Clinical Evidence Supporting Myo-Inositol in CKD

Although human trials specifically targeting myo-inositol in CKD are limited, preliminary evidence is promising. Observational studies and pilot clinical trials suggest improvements in:

• Estimated glomerular filtration rate (eGFR)

• Reduction in proteinuria

• Lower levels of serum creatinine

• Improved glycemic control in diabetic CKD

More large-scale, randomized controlled trials are needed, but the molecular evidence already supports its potential use as an adjunctive therapy.

Broader Health Benefits of Myo-Inositol

The utility of myo-inositol extends beyond renal disease. Its benefits span multiple organ systems:

Polycystic Ovary Syndrome (PCOS)

Myo-inositol is known to aid in insulin sensitivity and improved insulin utilization. This correlates with studies showing beneficial management of PCOS. It restores ovulation, improves insulin resistance, and normalizes androgen levels, offering a safe and effective alternative to pharmaceutical treatments.

Metabolic Syndrome

By improving insulin sensitivity, lowering triglycerides, and aiding weight loss, myo-inositol is a valuable tool in combating metabolic syndrome, a precursor to diabetes and therefore CKD and cardiovascular disease.

Mental Health and Neurological Disorders

Myo-inositol plays a role in brain signaling and has been explored in managing conditions like depression, anxiety, and bipolar disorder. Altered inositol metabolism has been observed in patients with mood disorders, and supplementation may help normalize neuronal activity.

Cancer Prevention

Preclinical studies suggest that myo-inositol has chemopreventive effects, especially in colon and lung cancer models. It modulates pathways involved in cell proliferation and apoptosis (programed cell death), offering potential in cancer risk reduction.

Safety and Dosage

Myo-inositol is generally considered safe, with minimal side effects even at high doses (up to 18 grams/day). Gastrointestinal discomfort is the most commonly reported adverse effect. For CKD and metabolic uses, doses typically range from 2 to 4 grams per day, divided into two administrations.

Potential Side Effects in CKD Patients

The potential side effects of myo-inositol in patients with CKD are generally mild and infrequent. Clinical evidence suggests that myo-inositol is well-tolerated, even at higher doses. The most commonly reported side effects include mild gastrointestinal disturbances such as nausea, flatus, and diarrhea, particularly at doses as high as 12 g/day.

In the context of CKD, there is no specific evidence indicating that myo-inositol causes significant adverse effects beyond these mild gastrointestinal symptoms. Studies have primarily focused on its renoprotective effects and its role in improving renal function and mitigating renal damage.

Given the potential benefits and the generally favorable safety profile, myo-inositol can be considered a viable adjunctive treatment in CKD, with careful monitoring for any gastrointestinal side effects. Further research may be needed to fully elucidate any long-term effects in this patient population.

Future Perspectives

As our understanding of cellular metabolism deepens, myo-inositol is positioned as a low-cost, low-risk, and multifaceted therapeutic agent. Future research may unlock:

• Optimized dosing strategies for CKD

• Combination therapies with anti-fibrotics or SGLT2 inhibitors

• Novel delivery methods for targeted renal therapy

• Its role in genetic kidney diseases, such as autosomal dominant polycystic kidney disease (ADPKD)

Conclusion

Myo-inositol offers exciting promise in slowing the progression of chronic kidney disease and combating other metabolic and inflammatory disorders. As a naturally occurring molecule with a strong safety profile, it represents a compelling adjunctive therapy. With continued research and clinical validation, myo-inositol may become a cornerstone in the management of chronic diseases, promoting longevity and improving quality of life.

References

1. Renoprotective Potential of Myo-Inositol on Diabetic Kidney Disease: Focus on The role of the PINK1/Parkin Pathway and Mitophagy Receptors. Sherkhane B, Kalvala AK, Arruri VK, Khatri DK, Singh SB. Journal of Biochemical and Molecular Toxicology. 2022;36(6):e23032. doi:10.1002/jbt.23032.

2. Myo-Inositol Attenuates Renal Interstitial Fibrosis in Obstructive Nephropathy by Inhibiting PI3K/AKT Activation. Hu X, Yang M, Li X, Gong Z, Duan J. Journal of Medicinal Food. 2023;26(6):368-378. doi:10.1089/jmf.2022.K.0152.

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4. Increased Urinary Osmolyte Excretion Indicates Chronic Kidney Disease Severity and Progression Rate. Gil RB, Ortiz A, Sanchez-Niño MD, et al. Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2018;33(12):2156-2164. doi:10.1093/ndt/gfy020.

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7. Myo-Inositol Attenuates Renal Interstitial Fibrosis in Obstructive Nephropathy by Inhibiting PI3K/AKT Activation. Hu X, Yang M, Li X, Gong Z, Duan J. Journal of Medicinal Food. 2023;26(6):368-378. doi:10.1089/jmf.2022.K.0152.

8. Role of Myo-Inositol in Acute Kidney Injury Induced by Cisplatin. Xie YH, Wang L, Li ML, Gong ZC, Du J. Toxicology. 2023;499:153653. doi:10.1016/j.tox.2023.153653.